1. Field of Invention
The field of the present invention relates generally to an inhaler device for aerosol delivery of medicine. More particularly, the present invention is directed to a device for improving medication compliance by providing feedback regarding correct and consistent usage of medicine inhalers to a patient and/or professional such as a physician, pharmacist, or therapist. The present invention is further directed to a method by which such professionals can track the usage of medicine inhalers between visits, and modify medicinal therapy based on downloading of this information to a clinical workstation allowing display and analysis.
2. The Prior Art
Getting patients to correctly use medicine inhalers is a major problem. Estimates indicate as few as one quarter of patients using inhalers do so correctly [Orehek, J., "Patient Error in Use of Bronchodilator Metered Aerosols," British Medical Journal, 1:76 (1976); Paterson, I. C. and G. K. Crompton, "Use of Pressurized Aerosols by Asthmatic Patients," British Medical Journal, 1:76-77 (1976); Saunders, K. B., "Misuse of Inhaled Bronchodilator Agents," British Medical Journal, 1:1037-1038 (1965); Shim, C., and M. H. Williams, "The Adequacy of Inhalation of Aerosol from Canister Nebulizers," The American Journal of Medicine, 69:891-894 (1980)]. In addition to unnecessary patient morbidity and mortality, an unfortunate consequence is that patients may stop taking their medications because they are not seeing any or enough benefit. Conversely, having failed to obtain expected benefits through prescribed usage, some patients will overuse medications and thereby increase the risk of side effects caused by higher than normal dosages (e.g., fungal infections in the mouth and throat or nervous system effects caused by medication absorbed in the gastro-intestinal tract).
These problems are especially evident in the case of aerosol pharmaceuticals delivered by hand-held inhalers. Hand-held metered dose inhalers (MDIs) are a preferred method of treatment for common respiratory ailments, since the delivery of medication directly to its intended site of action in the lungs allows a reduction in dosage by an order of magnitude or greater. However, certain of these compounds, such as anti-inflammatory corticosteroids, may take many weeks of administration before having a significant effect. Moreover, the inhalation and breath-holding maneuver required for successful delivery of aerosol to the lower airways is counterintuitive and poorly understood by most patients. Thus, a patient may be compliant in using the medication when prescribed, but unsuccessful in using it in the correct manner.
When therapeutic results are not obtained, it may not be evident to the physician which step(s) in the process are the problem. Relevent questions, for example, are "was the medication not taken at all?", "was it taken at the correct intervals and in proper relationship to exposure to allergens or other irritants?", and "was the inhalation performed correctly?".
Another problem the physician faces is how to interpret variability in therapeutic response. Is the variability due to some fundamental change in the patient's condition (e.g., the patient now has a low-grade upper respiratory infection) or is it caused by differences in delivered medication dosage?
Deposition of aerosol medication in the human lung is primarily determined by two processes, inertial impaction and gravitational sedimentation. Impaction of aerosols in the lungs occurs primarily at airway bifurcations, and has been shown in scintigraphic studies to increase as a function of flow rate. Sedimentation involves gravitational settling of aerosol particles on the airways and alveoli. Newman, S. P., Pavia, D., Garland, N. and S. W. Clarke, "Effects of Various Inhalation Modes on the Deposition of Radioactive Pressurized Aerosols," European J. Respiratory Dis., Supplement 119, 63:57-65, (1982) demonstrated that the percentage of aerosol deposited in the lungs of patients was significantly greater when the patients held their breath for ten seconds than when breath holding was only four seconds.
Thus, for aerosol to be deposited in the lower airways, the primary site of action for common medications such as corticosteroids and bronchodilators, the patient must coordinate the release of medication, inhale slowly enough to minimize loss of medicine through impaction in the throat and upper airways, and breath hold long enough to allow time for small particles to settle. In practice, this means an inhalation rate below one liter per second, and a breath hold for up to ten seconds.
A hand-held (e.g., metered or unit-dose) inhaler currently is a passive device that provides no information regarding the medication actually delivered. Orehek et al. found that only five of twenty asthmatic patients correctly inhaled. "The other 15 patients failed either to inspire deeply or hold their breath afterwards, or both, or poorly coordinated the puff and the inspiration." Orehek et al., "Patient Error in Use of Bronchodilator Metered Aerosols," British Medical Journal, 1:76, (1976).
For example, it has been found that in a group of 30 acute asthmatic patients directly observed in a clinical setting, 47% (14 patients) used incorrect technique. The fourteen patients with inadequate technique were then trained. Ten of them were retested after an interval of one day to one month. Five of the patients were still using their inhalers correctly; the other five had reverted to their original incorrect techniques. Shim, C., and M. H. Williams, "The Adequacy of Inhalation of Aerosol from Canister Nebulizers," The American Journal of Medicine, 69:891-894 (1980).
The device and approach described herein would have provided immediate feedback to the patients that they had reverted to incorrect use of their inhalers, and provided them with specific guidance as to what corrective action was required. Thus, retraining would not have had to wait until their next visit to the clinic.
The present approach also fosters the delivery of a uniform dose to the target sites of the patient's lungs upon each inhaler usage with the expectation of consistent therapeutic response. Thus, if the patient's symptoms or condition changes, the physician can evaluate the change with reasonable assurance that the difference is not simply due to a variation in medication dosage. By making data regarding the patient's inhaler use during the entire period between clinic visits available to the physician, therapy can be managed on a more informed basis.
It has been observed that, "The lung presents a significant barrier to the penetration of drug particles of a size small enough to maximize therapeutic efficacy." Padfield, J. M., "Principles of Drug Delivery to the Respiratory Tract", Drug Delivery to the Respiratory Tract, Ganderton, D., and Jones, T., ed., Horwood, London (1987). Padfield concludes "The design of delivery system for administering drugs to the lung can have as much, or more, impact as the choice of drug." (id.) Previous attempts to improve the effectiveness of aerosol medicine inhalers include a number of devices including spacers, aerosol holding chambers, flow-activated triggering mechanisms, and dry powder generators.
The problem of medicine deposition in the mouth and throat can be alleviated in some cases by the use of a tube spacer, an extension tube inserted between the metered unit-dose inhaler and the patient's mouth. This procedure still requires coordinated patient action and in itself provides no feedback to the patient as to the success or failure of the overall effort.
Another approach to improving MDI usage is the use of chambers or reservoirs into which the aerosol is discharged prior to inhalation. Such devices reduce the need for coordination of actuation and start of inhalation. A widely used device is described in Sackner, et. al., U.S. Pat. No. 4,484,577, 1984. This device also provides an audible whistle when the inspiration rate is above a fixed level. The device fails to address inter-patient variations in correct inhalation patterns, as well as the breath-holding stage. A common drawback of all chamber devices is their bulk. Such devices may not fit conveniently in a pocket or purse, and many patients are unwilling to use such large devices due to self-consciousness. The process in accordance with the present invention can be used irrespective of whether a tube spacer or a reservoir is used.
Conventional systems also include several inhaler devices which address the coordination problem by incorporating a means of triggering the medication release by the start of inhalation. Such devices have been described by Wass, U.S. Pat. No. 4,664,107 1987, and Johnson et. al., U.S. Pat. No. 4,803,978 1989. Shaner, U.S. Pat. No. 4,739,754, 1988 describes a "Suction Resistant Inhaler" whose design fosters a deep inhalation by the patient.
Other conventional devices have incorporated electromechanical components in order to record the timing and date of usage for review by a healthcare professional. Spector, et. al., "Compliance of Patients with Asthma with an Experimental Aerosolized Medication: Implications for Controlled Clinical Trials," Journal of Allergy & Clinical Immunology, 77:65-70 (1986) discloses the use of a nebulizer chronolog to record the patients' usage of MDIs between clinic visits. This incorporates a device for recording the time and date of each canister actuation for later review by physicians conducting research on patterns of patient compliance. This device lacks the capability for obtaining any information regarding the inspiratory maneuver itself. Furthermore, since the intention of the study was to record patients' MDI usage patterns without their knowledge, the device not provide any feedback to the patients regarding proper inhalation technique.
Similar devices are described by Rand et al., U.S. Pat. No. 4,817,822, 1989, and Dessertine, U.S. Pat. No. 5,020,527, 1991. The Rand device incorporates a mechanical rachet wheel and driving member to drive an indicator of the number of actuations of an aerosol canister. The Dessertine device provides a timer and a counter for tracking the number of and time between actuations.
In the aforementioned devices the time course of air flow is not measured, nor is it compared to the desired pattern for the specific patient as may be determined by a healthcare professional. Thus, these devices address only the aspect of compliance relating to if and when the medicine was used. In order to assess whether an aerosol medication has been used effectively, it is necessary to further determine information regarding the patient's coordination of actuation and inspiration, volume and flow rate of inspiration, and post-inspiratory breath holding.
In summary, conventional devices fail to adequately address the need for immediate patient feedback regarding multiple steps in the correct use of inhalers. These devices are also inadequate in providing information to both patient and healthcare professional regarding the critical factors which determine the success of medicine delivery, including coordination of inhalation with actuation, inhalation flow rate and duration of breath holding.
What is needed is a hand-held inhaler device which can monitor the complete time course of airflow during an inhalation, and which possesses the capability to guide the patient in its correct usage before, during, and after use. What is also needed is such an inhaler whose functions include the capacity to record relevent information about the timing and nature of its use for subsequent review by a healthcare professional.